Soluble factors as well as cellular reactions are known to mediate inflammatory and immune processes, but little is known of the endogenous factors that tend to limit these processes. We have demonstrated that an inhibitory factor(s) is present in normal human skin which interferes with T lymphocyte function. We postulate that during inflammatory reactions in skin, inhibitory factors are released from damaged epidermal keratinocytes and diffuse downward to limit the inflammatory reaction. This proposal is directed at further definition of the endogenous substance in skin which may act in vivo as a positive control of the limitation of immune and inflammatory reactions. We have located this endogenous inhibitor in the nuclear fraction of skin, and have shown that it can interfere with several assays of T lymphocyte function including mitogen induced blastogenesis and lymphocyte mediated cytotoxicity. We will characterize and confirm the inhibition of T cell function, and will investigate inhibitory effects on other leukocytes using cell separation techniques. The mechanism of inhibition will be studied via kinetic experiments, analysis of protein and RNA synthesis in affected cells, and by its effects on lymphocyte membrane markers and receptors. A cytotoxic assay using human keratinocytes as target cells will be developed to study the relevance of intracellular material release as a local inhibitor of inflammation. Lastly, this material will be solubilized and purified by standard biochemical techniques.